Over 2.7 million military personnel were deployed to Afghanistan, Iraq, and other countries in Southwest Asia and exposed to high levels of particulate matter ?2.5 m in diameter (PM2.5, particles small enough to deposit in the small airways and alveoli) from frequent dust storms, burn-pit smoke (waste burning), and poorly regulated industrial and vehicular sources. Previous studies have reported that deployed personnel have experienced symptoms consistent with chronic respiratory disease. However, objective evidence of exposure- related health effects is limited. To address this concern, VA Cooperative Study #595 ?Service and Health Among Deployed Veterans (SHADE)? is being conducted to examine the hypothesis that greater cumulative exposure to PM2.5 while deployed is associated with lower lung function assessed by spirometry. A key strength of SHADE is an exposure assessment approach that will use historical satellite and regional visibility records to reconstruct deployment-related PM2.5 in 5000 Veterans assessed at 6 centers. A limitation of spirometry is that it is insensitive to early lung disease. This proposal is one of three collaborative projects to systematically examine the pulmonary consequences of exposure during deployment. We will conduct additional assessments in a subset of 280 SHADE participants at four sites (Seattle, Boston, Minneapolis, and Houston) both with and without respiratory symptoms (cough, wheeze, dyspnea) as assessed on the CSP #595 respiratory health questionnaire, and with little smoking history (former smokers with <10 pack years or never smokers). Our hypothesis is that exposure to PM2.5 during deployment to Southwest Asia and Afghanistan is associated with early and often undiagnosed pulmonary diseases. In the VA Puget Sound proposal, we will complete 3 additional lung physiology measurements to assess for abnormalities in gas exchange and in small airways function that could indicate early lung disease. We will measure the diffusing capacity for carbon monoxide (DLCO), a breath test that indirectly measures oxygen transfer from air to blood, and is a marker of gas exchange abnormality and lung injury. We will also measure two clinical tests that examine small airways function: (1) impulse oscillometry which uses forced oscillations to measure small airways resistance (R5-R20), and (2) nitrogen multiple breath washout test to determine the lung clearance index, a measure of ventilation heterogeneity. The MBW test also provides the functional residual capacity, a measure of lung volumes not available with spirometry alone. We will examine whether these clinical tests are associated with respiratory symptoms and air pollution during deployment (PM2.5). In addition to the physiologic tests in this proposal, as part of the overall collaborative proposal, participants will also have: (a) structural assessment of the lung by CT scan (project led by Dr. Garshick at the Boston VA) and (b) assessment of systemic biomarkers and immune cell activation (project led by Dr. Wendt at the Minneapolis VA, and Dr. Kheradmand at the Houston VA). Using the CT data from the Boston VA project, this proposal will examine the relationship between DLCO, R5-R20, and LCI with CT structural abnormalities such as emphysema and gas-trapping. In the collaborative analysis, we will test the hypothesis that greater exposure to deployment-related PM2.5 results in specific airway and lung parenchymal endotypes that could be distinguished by functional, structural, and biochemical mechanisms. Our three coordinated proposals will complement CSP #595 by comprehensively characterizing early deployment-related lung findings related to PM2.5 exposure that may in the future be used to assess disease. By identifying different exposure-related disease types, this research will help in the recognition and treatment of Veterans with deployment-related lung disease.